Haemostasis stuff Flashcards
From anatomy and physiology, includes haemostasis content
1
Q
Haemostasis
A
- The cessation/stopping of bleeding (Normal response)
- General process:
1) Injury, vessel spasm (Vasoconstriction) + collagen is exposed
2) Platelet Plug Formation
3) Coagulation
4) Clot retraction
5) Fibrinolysis
2
Q
Haemorrhage
A
The excessive flow of blood (Pathogenic response)
3
Q
Blood vessel anatomy
A
- Tunica intima = The innermost layer of the blood vessel, made up of 1 cell thick endothelial cells
- Tunica media = Where smooth muscle resides
- Tunica externa = Outermost tunica layer
- Arteries + Veins contain all 3, whereas the capillaries only have tunica intima to allow gaseous exchange pathway
4
Q
Vessel Spasms
A
- Also known as vasoconstriction
- Direct smooth muscle cell damage triggers vasoconstriction, triggering pain receptors too
- Vasoconstriction helps slow down the leak of blood out of the wound
5
Q
Platelets active vs dormant state
A
- At rest, platelets have a discoid shape, but develop pseudopodia when activated, which can enable it to form 2 forms:
+ Filopedia
+ Followed by lamelliopedia, allowing it cover the wound
6
Q
Platelet agonists
A
- Each agonist has a different degree of “strength” to activate the platelets
- The stronger the platelet agonist, the more likely platelet activation will happen and stronger the response
- Strong agonists: Collagen, Thrombin
- Intermediate agonists: Thromboxane A2
- Weak: ADP, Platelet Activating Factor, Adrenaline, Vasopressin, Serotonin
7
Q
Platelet Plug Formation (PPF)
A
- 4 steps
1) Adhesion
2) Activation
3) Secretion
4) Aggregation
8
Q
Platelet Plug Formation: Adhesion
A
- First step of PPF
- Happens when collagen fibres become exposed and the Von WIllebrand Factor (VWF) binds to the collagen
+ VWF is a plasma protein, just like any other plasma protein flows freely around the body - VWF binding to the collagen then allows it to bind to the platelet via the GlycoproteinIb(GPIb)-V-IX complex, slowing down the platetlet’s movement so it rolls on the surface of the collagen
9
Q
Platelet Plug Formation: Activation (Some Secretion + Aggregation)
A
- Second step of PPF
- As the platelet rolls, its other receptors also come into contact with the collagen, including GPVI (GP6)
- When GPVI touches collagen, it triggers a signalling cascade inside the platelet, leading to the release of Ca from its stores, increasing Ca concetration in the platelets, which has 3 effects:
+ Shape morphing: Discoid -> lamellipodia
+ Degranulation of alpha-granules + dense granules to recruit other nearby platelets or have an autocrine effect on the secreting platelet (+tive feedback for both outcomes)
+ Aggregation
10
Q
Platelet Plug Formation: Secretion
A
- Third step of PPF
- Dense granules contents:
+ ADP
+ Serotonin - Alpha-granules contents
+ Fibrinogen
+ VWF - Cytoplasmic Thromboxane A2 also secreted
- These all contribute to the +tive feedback loop
11
Q
Platelet Plug Formation: Aggregation
A
- Fourth step of PPF
- The buildup of Ca in the platelet changes the shape of alpha2b/beta3 receptors on platelet surface
+ Alpha2b/beta3 are an example of integrin, receptors that have a low affinity (inactive) shape along with a high affinity (active) shape, which when active binds to fibrinogen (respective ligand) - Fibrinogen binds to 2 alpha2b/beta3 on 2 separate platelets, cross-linking them together, causing aggregation
- Secretion of fibrinogen means more cross-links can take place
12
Q
Negative regulation of platelets
A
- Majority of the time, the body is actively silencing platelets when they are not needed
- This is done by Prostacyclina nd Nitric Oxide (NO) secreted by healthy endothelial cells
- These chemicals are released into the bloodstream as platelets pass, keeping them inactive
- If endothelium is damanged, platelets are more likely to become active, increasing risk of thrombosis
13
Q
Coagulation
A
- The process in which the fluid blood is converted into a gelatinous clot
- Helps convert the platelet plug structure into a more stable clot, formation of the scab caused by clot being exposed to air, causing it to dry out
14
Q
Fibrin
A
- A polymer protein made up of fibrinogen monomer units
- Fibrinogen monmer can bind to alpha2b/beta3 receptors on 2 different platlets to aggregate the platelets
- To form fibrin, thrombin (preotease) catalyses the conversion of fibrinogen into fibrin
+ Cuts out fibrinopeptides, creating a site for monomers to bind together
15
Q
Thrombin
A
- Protease that catalyses fibrinogen conversion
- Circulates in precursor form (Prothrombin) in the plasma
- Can also trigger platelet activation
- To become active, prothrombin is cleaved to generate thrombin via intrinsic or extrinisc pathway
- Difference between intrinsic + extrinsic pathway is that the extrinsic pathway requires endothelial cells to release tissue factor after injury
